Discrete dosages of pharmaceutical compositions suitable for oral administration are conveniently administered as solid dosage forms, typically tablets. In addition to the therapeutic ingredient or ingredients (commonly referred to as “actives,” “active pharmaceutical ingredients,” or “API”), the tablet comprises pharmaceutically acceptable materials, known as excipients, that are not actives and do not provide a therapeutic effect, but are added to the tablet formulation to confer specific properties not related to the activity of the active.
There are three general methods of preparation of tablets: (1) direct compression or tabletting; (2) dry granulation; and (3) wet granulation. In direct compression, the powdered material(s) to be included in the tablet (including the active and the excipients) are blended together and compressed directly without intermediate processing such as granulation. Dry granulation procedures may be used where poor flow or low bulk density of the direct compression mix precludes direct compression. The method includes mixing the ingredients, roller compacting or slugging the mix, dry screening or milling the coarse dry granuloate, lubricating and finally compressing the lubricated granules. The wet granulation procedure includes mixing some or all of the ingredients of the dosage form and thereafter adding solutions of a binding agent to the mixed powders to obtain a granulation. Thereafter, the damp mass is screened, and dried, e.g., via tray drying, the use of a fluid-bed dryer, spray-dryer, radio-frequency dryer, microwave, vacuum, or infra-red dryer.
Because direct compression requires fewer unit operations than wet granulation, it is a less expensive process. This means less equipment, lower power consumption, less space, less time, and less labor leading to reduced production cost of tablets. However, direct compression is limited to those situations where the compression mix has the requisite physical characteristics required for formation of a pharmaceutically acceptable tablet. Because the tablet formulation is compressed to prepare the tablet, the formulation must possess physical characteristics that lend themselves to processing in such a manner. Among other things, the tablet formulation must be free-flowing, must be lubricated, and, importantly, must possess sufficient binding to insure that the tablet remains intact after compression.
Tablets are formed by the application of pressure to the tablet formulation on a tablet press. A tablet press includes a lower punch which fits into a die from the bottom and an upper punch having a corresponding shape and dimension, which enters the die cavity from the top after the tablet formulation fills the die cavity. The tablet is formed by pressure applied on the lower and upper punches. The ability of the tablet formulation to flow freely into the die is important in order to insure that there is a uniform filling of the die and a continuous movement of the tablet formulation from its source. The tablet must also eject cleanly from the die following compression. Typically, a lubricant is added to the tablet formulation to avoid sticking to the die and to cause the formulation to flow freely.
Because of its inherent compactability characteristics, microcrystalline cellulose (MCC) is widely used as an excipient in tablet formulations. Good binding and disintegration properties are obtained with microcrystalline cellulose when used it is used in direct compression tablet formulations. However, microcrystalline cellulose can have lubricant sensitivity. Lubricant sensitivity refers to the reduction in bonding between the plastically-deforming particles in the powder due to the addition of lubricant, which leads to reduction in tablet strength or hardness. Lubricant sensitivity is the ratio of the unlubricated compactability of the tablet formulation to the lubricated compactability of the tablet formulation.
Tablet manufacturing has changed by the introduction of the direct compression process and high-speed machines. These two developments have increased the demands on the functionality of excipient in terms of flow and compression properties. Thus, a need exists for an excipient with superior functionalities particularly high compactability, low lubricant sensitivity, and low ejection force profile that makes it an ideal candidate for tablet formulations, particularly for direct compression.